Proteins of the Ly6 family have a low-molecular weight GPI-anchored structure and have been identified as a class of cell surface glycoproteins forming a gene cluster on mouse chromosome 15 [Proc. Natl. Acad. Sci., USA., 84, 1638-1643 (1987)].
The Ly6 family is specifically expressed at high levels in bone marrow cells and lymphoid cells and, therefore, has been utilized as a marker for T-cell differentiation and hematopoietic stem cells [Immunol. Cell Biol., 73, 277-296 (1995)]. While much remains to be known about its functions in vivo, the finding that its expression is highly modulated in the lymphocytic system suggests that these proteins are playing important roles in the immune system, particularly in the differentiation and function of T cells. It is reported that Ly6c, for instance, mediates the homing of CD8+ T cells to the lymph node through integrin-dependent adhesion [Proc. Natl. Acad. Sci., USA., 94, 6898-6903 (1997)].
Furthermore, many GPI-anchored proteins are known to interact with protein kinases [Science, 254, 1016-1019 (1991)]. For example, the interaction of Ly6 with p56lck and p59fyn suggests the likelihood of its involvement in the signal transduction of T cells [Eur. J. Immunol., 23, 825-831 (1993)]. It is also reported that T cells derived from Ly6a-defective mice have been enhanced in the ability to proliferate in response to antigenic stimulation [J. Exp. Med., 186, 705-717 (1997)]. The possibility of its regulating not only the activation of T cells but also that of B cells has also been suggested [J. Immunol., 144, 2197-2204 (1990)].
Furthermore, several GPI-anchored proteins are known to have been expressed and be functioning in both the lymphocytic system and the nervous system [Nature, 379, 826-829 (1996); Curr. Biol., 7, 705-708 (1997)]. In the Ly6 family, Ly6a.2 and Ly6E are reportedly present and functioning in both systems [Proc. Natl. Acad. Sci., USA., 85, 2255-2259 (1996); J. Immunol, 157, 969-973 (1996)].
Elucidation of the physiological roles played by such proteins of the Ly6 family and the genes coding for the proteins and the resulting information are considered to be of use in the field of fundamental scientific research as well as in the pharmaceutical field in connection with the purification of blood stem cells, studies on the differentiation of blood cells, activation of immune cells, inhibition of activation of immune cells, therapy of tumors, and the like.
Recently, in patients with Alzheimer's disease, an excessive cerebral temperal lobe atrophy as compared with age-associated brain atrophy has been reported [Jobst, K. A., et al., Lancet, 343, 829-830 (1994)], suggesting that some gene or genes having a bearing on the cerebral temperal lobe are somehow associated with the onset and progression of Alzheimer's disease. It is logical to assume that should such a gene be identified or characterized, there might be provided information useful for the therapy and prophylaxis of Alzheimer's disease.
Therefore, an object of the present invention is to provide the above information needed by those concerned, particularly a novel human protein belonging to the Ly6 family and a gene coding for the protein.
A further object of the invention is to provide a pharmaceutical composition for the therapy and prophylaxis of various neurodegenerative diseases, represented by Alzheimer's disease.
The present inventor explored into the genes derived from various human tissues and succeeded in isolating and characterizing a novel brain-specific gene meeting the above objects. The inventor further found that the level of expression of this newly isolated gene is markedly depressed in the temperal lobe, inclusive of the hippocampus and entorhinal cortex, of a patient with Alzheimer's disease, that this is a causative factor in the onset and progression of Alzheimer's disease and in dementia and other disturbances and that this gene and its expression product can be exploited with advantage in the therapy and prophylaxis of Alzheimer's disease. The present invention has been accomplished on the basis of the above findings.